The basic mechanisms by which several psychopharmacological agents alter behavior in man are not well understood. Lysergic acid diethylamide, serotonin, mescaline, bufotenine, and harmine were shown by the principal investigator to affect neuromuscular activity and metabolism of the liver fluke, Fasciola hepatica. There is a high degree of correlation between the psychomimetic potencies of lysergic acid derivatives in man and their neuromuscular effects in the flukes. The basic philosophy of this project is that the more we know about the biochemical effects of these agents, in systems lower than mammals such as the liver fluke, the better will be our chance to understand the effects of these agents in man as well as the mechanisms involved in psychosis. Our basic approach is to study the effect of psychopharmacological agents in the liver fluke, and to compare these effects with homologous systems in the mammalian brain or other tissues. We plan to study the mechanism of activation of adenyl cyclase in the fluke by serotonin, LSD and other agents; to isolate and purify the catalytic and the hormonal components of the system; and to study the kinetics and properties of this system in the mammalian brain in order to identify the differences and similarities between the two systems. We will attempt to answer the question whether there is any relationship between levels of cyclic AMP in the fluke or in the mammalian brain, and the pharmacological effects of these agents. Experiments will also be carried out to study the properties of the serotonin neurones in the fluke and how they compare pharmacologically with serotonin neurones in the mammalian brain. We intend to isolate the LSD - serotonin receptor(s) from the flukes, to study the nature of interaction between different psychopharmacological agents and these receptors, and to study the physio-chemical properties of the receptors. Studies on the biochemical and molecular properties of chemotaxis (cell or organisms attraction to chemicals and to other cells) and the effect of psychopharmacological agents on this process will be carried out. BIBLIOGRAPHIC REFERENCES: Abrahams, S. L., Northup, J. K. and Mansour, T. E. Adenosine Cyclic 3', 5'-Monophosphate in the Liver Fluke, Fasciola Hepatica. I Activation of Adenylate Cyclase by 5-Hydroxy-tryptamine. Mol. Pharmac (Text Truncated - Exceeds Capacity)